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Biomedical subjects

M Shimizu

Publications and source records attributed to M Shimizu.

At least 145 records · Page 8Linked to original sources

Possibility of sialographic sonography: a Doppler phantom study.

OBJECTIVES: The purpose of this study was to develop a new diagnostic method that has the merits of both sialography and sonography. STUDY DESIGN: Saline solution and various contrast media (Urografin 76%; 100%, 90%, and 67% Lipiodol Ultra-Fluide; 5% and 1% barium sulfate; and Levovist) were injected into thin tubes at a rate of approximately 0.001 to 0.1 mL/s. The relationship between the Doppler signal intensity and the kind, concentration, and velocity of the fluid was analyzed. RESULTS: Levovist, 90% and 67% Lipiodol Ultra-Fluide, and the barium sulfate solutions produced Doppler signals. The mixture of Lipiodol Ultra-Fluide and saline solution produced high signals at any concentration, in contrast with the barium sulfate solutions. Signals could be observed at any speed, from the speed of normal sialography down to 0.001 mL/s, and there was a proportional relationship between signal intensity and velocity for all fluids producing signals. CONCLUSION: The fact that we could obtain high signals with several fluids indicates potential clinical diagnostic usefulness of sialographic sonography.

Barium Sulfate↗

The combined use of US and MR imaging for the diagnosis of masses in the parotid region.

PURPOSE: To evaluate the usefulness of the combination of the two non-invasive modalities US and MR imaging to diagnose masses in the parotid region. MATERIAL AND METHODS: The US and MR findings of 21 patients with parotid masses were analyzed retrospectively by two radiologists without any clinical or histopathological information. The specific points evaluated were location, shape, margin, internal architecture, and intensity level on both US and MR, posterior echo enhancement on US, and capsule-like lining of the tumor on MR. RESULTS: The findings concerning the shape and margin on US and MR were in fairly good agreement. Concerning the findings of the internal architecture, US could reveal the minute structures of the tumor while MR demonstrated differences in the signal intensities of histological tissue types of the various tumors. The posterior echo enhancement on US and the capsule-like lining on MR of the tumors were also useful for the diagnosis. CONCLUSION: Our results suggest that the combination of US and MR is useful for examining soft tissue masses in the parotid region to make a more accurate diagnosis, and not just differentiate malignant lesions from those which are benign.

Adolescent↗

Chromatin structure of yeast minichromosomes containing triplet repeat sequences associated with human hereditary neurological diseases.

Expansion of triplet repeat sequences such as (CTG)n, (CGG)n, and (GAA)n causes human genetic diseases. Since DNA is packaged into arrays of nucleosomes in eukaryotic cells, chromatin may be involved in the mechanism of triplet repeat diseases. To elucidate this issue, we have examined effects of triplet repeat sequences on the chromatin organization in vivo using well defined yeast minichromosomes. We show here that (CGG)12 disrupts an array of positioned nucleosomes, whereas (CTG)12 promotes the nucleosome formation. Thus, triplet repeat sequences can affect the chromatin organization in vivo, which may contribute to the triplet repeat expansion or alterations in the expression of genes associated with triplet repeat diseases.

Chromosomes, Fungal↗

How does heme axial ligand deletion affect the structure and the function of cytochrome b(562)?

We have recently generated a new mutant of cytochrome b(562) (cytb(562)) in which Met7, one of the axial heme ligands, is replaced by Ala (M7A cytb(562)). The M7A cytb(562) can bind heme and the UV-visible absorption spectrum is of a typical high-spin ferric heme. To investigate the effect of the lack of Met7 ligation on the structural integrity of cytb(562), thermal transition analyses of M7A cytb(562) were conducted. From the thermodynamic parameters obtained, it is concluded that the folding of M7A cytb(562) is comparable to the apoprotein despite the presence of heme. On the other hand, exogenous ligands such as cyanide and azide ions are readily bound to the heme iron, indicating that the axial coordination site is available for substrate binding. The peroxidase activity of this mutant is thus examined to evaluate new enzymatic function at this site and M7A cytb(562) was found to catalyze an oxidation reaction of aromatic substrates with hydrogen peroxide. These observations demonstrate that the Met7/His102 bis-ligation to the heme iron is crucial for the stable folding of cytb(562), whereas the functional conversion of cytb(562) is successfully achieved by the loose folding together with the open coordination site.

Amino Acid Substitution↗

Anaplastic lymphoma kinase expression in inflammatory pseudotumors.

Anaplastic lymphoma kinase (ALK), a hallmark of anaplastic large cell lymphoma, has recently been implicated in the genesis of some inflammatory pseudotumors (inflammatory myofibroblastic tumors) in children and young adults. The aim of this study was to determine the frequency of its expression among inflammatory pseudotumors, and to characterize the clinicopathologic features of the positive cases. Sixty-one cases of inflammatory pseudotumors were retrieved from the surgical pathology archives and consultation files. Paraffin sections were immunostained with the antibody ALK1. The patients ranged in age from 0.5 to 79 years (median age, 50 years), with 10 patients (16.4%) younger than 20 years. Five cases (8.2%) were ALK+, including two of six urogenital inflammatory myofibroblastic tumors, none of eight pulmonary inflammatory pseudotumors, three (one adrenal, one small bowel, one liver) of 31 extrapulmonary inflammatory pseudotumors, none of nine hepatic/splenic inflammatory pseudotumors expressing follicular dendritic cell markers and harboring Epstein-Barr virus, and none of seven inflammatory pseudotumors of the lymph node. When only those patients 40 years or younger were considered, the ALK positivity rate became 21.7% (five of 23). All five ALK+ cases occurred in young patients aged 0.5 to 37 years, who were alive and well at 3.5 to 17 years. The tumors exhibited a spectrum of histologic features typical of inflammatory pseudotumors/myofibroblastic tumors, but there was at least focal nuclear atypia. Immunostaining for ALK produced fibrillary or granular cytoplasmic staining in the neoplastic cells, sometimes with cell membrane accentuation. This study confirms that ALK is implicated in a proportion of inflammatory pseudotumors, and is generally associated with a favorable outcome. The results also support the heterogeneity of inflammatory pseudotumors, with the follicular dendritic cell/Epstein-Barr virus-positive cases and those occurring in lymph nodes representing different biologic entities.

Adolescent↗

Quantitative assessment of diffuse coronary artery disease using a three-dimensional reconstruction method compared with intravascular ultrasound images.

BACKGROUND: It can be difficult to estimate the degree of stenosis in patients with diffuse coronary artery disease (CAD), because of the lack of a normal reference segment. If the size of normal coronary lumen has a direct relation to size of distal myocardial bed, it could be used to estimate the 'normal' cross-sectional area of coronary lumen. Accordingly, we could estimate the degree of stenosis of coronary arteries with diffuse disease by comparing them with calculated 'normal' areas of lumen. OBJECTIVE: To assess the validity of the above hypothesis. METHOD: Fourteen subjects without coronary atherosclerosis (group A) and 16 patients with CAD (group B) underwent simultaneous bidirectional coronary arteriography. Using these coronary arteriograms, we determined the relationship between cross-sectional area of coronary lumen measured by using a computerized edge-detection system and summed distal branch length calculated by using our computerized three-dimensional reconstruction method. RESULTS: For group A, we found a close correlation between area of lumen and branch length (r= 0.948). However, for group B, there were some segments for which the measured area of lumen was clearly smaller than that expected from the relationship for group A. From this relationship for group A, we calculated the stenosis ratios of 22 segments and, to confirm their accuracy, we compared the stenotic ratios with those measured on intravascular ultrasound images. The stenotic ratio of each segment of stenotic coronary artery calculated by our method agreed significantly well with the results obtained from the ultrasound measurements (r= 0.980). CONCLUSIONS: These observations validate a novel approach to quantifying diffuse CAD using clinical arteriograms.

Case-Control Studies↗

CPT-11 alters the circadian rhythm of dihydropyrimidine dehydrogenase mRNA in mouse liver.

Combination chemotherapy consisting of 5-fluorouracil (5-FU) and 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carboxycamptothecin (CPT-11) is a promising regimen for gastrointestinal cancer. The circadian-dependent efficacy and toxicity of 5-FU are related to the circadian variation in the activity of dihydropyrimidine dehydrogenase (DPD), which is a rate-limiting enzyme in the pyrimidine catabolic pathway. To optimize the schedule of the CPT-11 plus 5-FU combination, we investigated the effect of CPT-11 on the circadian rhythm of DPD in vivo. In control mice, the DPD mRNA level in the liver was significantly higher at 14:00 than that at 02:00. After intravenous administration of CPT-11 (30 mg / kg) at 20:00, the circadian rhythm of the DPD mRNA level in the liver was no longer observed 18 h later (14:00), but it was unaffected 6 and 18 h later (at 14:00 and 02:00) when CPT-11 was given at 08:00. In addition, a dose-dependent lengthening of the period of the circadian rhythm of DPD was observed for 42 h after intravenous injection of CPT-11 at 20:00. The levels of DPD protein and activity at 21 h after administration of CPT-11 (at 17:00) were significantly higher than at 9 h (at 05:00). These results suggest that CPT-11 may influence the circadian rhythm of DPD at the transcriptional level. Modulation of the circadian rhythm of DPD by CPT-11 may be a factor in optimizing the combination of 5-FU and CPT-11.

Animals↗

Suppression of occurrence and advancement of beta-catenin-accumulated crypts, possible premalignant lesions of colon cancer, by selective cyclooxygenase-2 inhibitor, celecoxib.

Suppression of occurrence and advancement of premalignant lesions is important for cancer prevention. Our previous studies clarified that beta-catenin-accumulated crypts, independent of aberrant crypt foci (ACF), are probably direct precursors of colon cancers in rats. Here we investigated the effects of a selective cyclooxygenase-2 inhibitor, celecoxib, on the development of beta-catenin-accumulated crypts in comparison with those on ACF. Male F344 rats were divided into 4 groups. Groups 1 - 3 were administered azoxymethane (AOM) s.c. at a dose of 15 mg / kg body weight, once weekly for 3 weeks to induce beta-catenin-accumulated crypts. Groups 2 and 3 also received experimental diet containing celecoxib (500 and 1500 ppm, respectively) for 8 weeks, starting a week before the first dosing of AOM. At termination, the frequency and crypt multiplicity (number of crypts / lesion) of beta-catenin-accumulated crypts of groups 2 and 3 were significantly less than that of group 1. Furthermore, numbers of silver-stained nucleolar organizer regions (AgNORs) / nucleus in beta-catenin-accumulated crypts were also decreased by exposure to celecoxib. In this study, celecoxib had greater effects on the frequency and growth of beta-catenin-accumulated crypts than on those of ACF. These findings represent additional evidence that beta-catenin-accumulated crypts are premalignant lesions of colon cancer. The results also suggest that beta-catenin-accumulated crypts could be a novel target for evaluation of possible chemopreventive agents against colon carcino-genesis, and indicate that possible chemopreventive effects of celecoxib on the initial stage of colon carcinogenesis may be related to modulation of cell proliferation activity in such early lesions.

Animals↗

Marked potentiation of activity of beta-lactams against methicillin-resistant Staphylococcus aureus by corilagin.

We found that an extract of Arctostaphylos uva-ursi markedly reduced the MICs of beta-lactam antibiotics, such as oxacillin and cefmetazole, against methicillin-resistant Staphylococcus aureus. We isolated the effective compound and identified it as corilagin. Corilagin reduced the MICs of various beta-lactams by 100- to 2,000-fold but not the MICs of other antimicrobial agents tested. The effect of corilagin and oxacillin was synergistic. Corilagin showed a bactericidal action when added to the growth medium in combination with oxacillin.

Anti-Bacterial Agents↗

Upregulation of fractalkine in human crescentic glomerulonephritis.

BACKGROUND/AIM: To evaluate the importance of fractalkine, a novel member of the CX3C chemokine, and natural killer (NK) cells in human crescentic glomerulonephritis, we determined the presence of fractalkine in the diseased kidneys immunohistochemically, and the correlation among fractalkine, NK cells and the degree of renal damage. METHODS: Twenty-three patients (13 males and 10 females) with primary or secondary crescentic glomerular disease were evaluated in this study. Fractalkine and CD16-positive cells including NK cells were detected immunohistochemically. RESULTS: Fractalkine-positive cells were detected in the interstitium of 23 patients with crescentic glomerulonephritis, while they were not detected in the glomeruli. In addition, CD16-positive cells were detected in both the glomeruli (1.3 +/- 0.2/glomerulus) and interstitium (1.3 +/- 0.2/visual field). The number of fractalkine-positive cells in the interstitium correlated with the number of CD16-positive cells before glucocorticoid therapy (r = 0.43, p = 0.047, n = 23). The number of fractalkine-positive cells in the interstitium before glucocorticoid therapy (0.2 +/- 0.1/visual field) decreased after therapy (0.1 +/- 0.1/visual field, p = 0.050) in 11 cases tested. The number of CD16-positive cells in the diseased kidneys did not change after glucocorticoid therapy. CONCLUSION: These results suggest that the local production of fractalkine may explain the presence of CD16-positive cells including NK cells, which may participate in the interstitial lesions of human crescentic glomerulonephritis before corticoid therapy.

Adult↗

A rare case of bronchial glomus tumor.

A 48-year-old man was admitted because of bloody sputum in whom a chest computed tomography (CT) scan and fiberoptic bronchoscopy demonstrated a polypoid tumor in the left main bronchus. The tumor was surgically resected, and the pathological and immunohistochemical findings led to diagnosis of the tumor as a bronchial glomus tumor.

Biopsy, Needle↗

Theophylline metabolism after cardiac surgery.

The effect and metabolism of theophylline administration after cardiac surgery has never been reported. Two series of 2-hour intravenous aminophylline administrations (3 mg/kg/h) were conducted in 10 adult patients on the operative day (acute phase) and on the 4th or 5th postoperative day (recovery phase). Both blood and urine samples were collected for 24 hours after dosing. Heart rate increased in both phases, but the cardiac index increased with the decrease of diastolic blood pressure only in the acute phase (p < 0.05). Plasma concentration levels of theophylline tended to be slightly higher in the acute phase, and renal clearance increased in the recovery phase (p < 0.05). The urinary ratio of 3-methylxanthine to theophylline was significantly higher in the acute phase (p < 0.05). This suggests that cytochrome P4501A2 is partially activated rather than depressed and that N-demethylation is promoted more than hydroxylation immediately after surgery.

Adult↗

Enhanced activity in parathyroid hormone-(1-14) and -(1-11): novel peptides for probing ligand-receptor interactions.

The amino-terminal portion of PTH is critical for PTH-1 receptor (P1Rc) activation. In exploring this component of the ligand receptor interaction, we recently showed that the agonist potency of the weakly active PTH-(1-14)NH(2) peptide can be enhanced by natural amino acid substitutions at several positions, including position 11 (normally leucine). Here we show that the potency of PTH-(1-14)NH(2) can be enhanced by using nonnatural amino acids that increase the length and polarizability of the position 11 side-chain. Thus, in LLC-PK(1) cells stably expressing high levels of the human P1Rc, [homoarginine([Har)(11)]PTH-(1-14)NH(2) was 30-fold more potent for cAMP production than was native PTH-(1-14)NH(2). Combining the homoarginine-11 substitution with other recently identified activity-enhancing substitutions yielded [Ala(3,12),Gln(10),Har(11),Trp(14)]PTH-(1-14)NH(2), which was 1500-fold more potent than PTH-(1-14)NH(2) (EC(50) = 0.12 +/- 0.04 and 190 +/- 20 microM, respectively) and only 63-fold less potent than PTH-(1-34) (EC(50) = 1.9 +/- 0.5 nM). The even shorter analog [Ala(3),Gln(10),Har(11)]PTH-(1-11)NH(2) was also a full cAMP agonist (EC(50) = 3.1 +/- 1.5 microM). Receptor mutations at Phe(184) and Leu(187) located near the boundary of the amino-terminal domain and transmembrane domain-1 severely impaired responsiveness to the PTH-(1-11) analog. Overall, these studies demonstrate that PTH analogs of only 11 amino acids are sufficient for activation of the PTH-1 receptor through interaction with its juxtamembrane region.

Amino Acid Sequence↗

(10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3: an improved synthesis via 19-nor-10-oxo-vitamin D.

An efficient synthetic route to (10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3 was developed. The key feature of this pathway is the introduction of a 19-fluoromethylene group to a (5E)-19-nor-10-oxo-vitamin D derivative. The 10-oxo-compound was obtained via a 1,3-dipolar cycloaddition reaction of (5E)-1alpha,25-dihydroxyvitamin D with in situ generated nitrile oxide followed by ring cleavage of the formed isoxazoline moiety with molybdenum hexacarbonyl. Conversion of the keto group of (5E)-19-nor-10-oxo-vitamin D to the E and Z fluoromethylene group was achieved through a two-step sequence involving a reaction of lithiofluoromethyl phenyl sulfone followed by the reductive desulfonylation of the alpha-fluoro-beta-hydroxy sulfone. The dye-sensitized photoisomerization of the (5E)-19-fluorovitamin D afforded the desired (5Z)-19-fluorovitamin D derivatives, (10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3.

Calcifediol↗

Coronary lesion morphology and prognosis in young males with myocardial infarction with or without familial hypercholesterolemia.

The present study examined the angiographic characteristics and prognosis of young males under 40 years of age with acute myocardial infarction (AMI) and familial hypercholesterolemia (FH). The study group was divided into an FH group (n=16) and a non-FH group (n=27). Lesion morphology was classified as complex or smooth. Overall 36 patients were followed up for an average of 9.4 years. The frequency of angiographic normal or nonobstructive culprit lesions was significantly higher in the non-FH group (p<0.01). In contrast, the incidence of complex or totally occlusive lesions was higher in the FH group (p<0.01). At 10-year follow-up, survival rates from cardiac death (FH 85% vs non-FH 100%, p=0.06), from AMI (FH 43% vs non-FH 80%, p<0.05), and from any ischemic event at a new lesion (FH 9% vs non-FH 67%, p<0.01) were all reduced in the FH group. These results suggest that the mechanism of AMI in young male patients with FH differs from that in similar aged patients without FH, and that the overall prognosis of these patients is less favorable.

Adult↗

Systolic dysfunction and blood pressure responses to supine exercise in patients with hypertrophic cardiomyopathy.

Left ventricular function and blood pressure responses were evaluated in 56 patients with non-obstructive hypertrophic cardiomyopathy (HCM) and 12 control subjects by using a radionuclide ventricular function monitor during supine ergometer exercise. Patients with HCM were divided into 2 groups: (i) group A had no decrease in ejection fraction (EF) during exercise; and (ii) group B had a decrease in EF during exercise. During exercise, the change in end-diastolic volume did not differ between the 3 groups. In contrast, the change in end-systolic volume differed between the 3 groups (p<0.0001). The change in systolic blood pressure (SBP) also differed significantly between the 3 groups. The change in SBP in group B was smaller than that in the control group and group A, and changes in the EF and changes in the SBP between rest and peak exercise showed a significant correlation (p<0.005). These results suggest that exercise-induced systolic dysfunction in patients with non-obstructive HCM may contribute to abnormal blood pressure response in those patients.

Adult↗

Arrhythmias in patients with Brugada-type electrocardiographic findings.

Brugada syndrome is characterized by marked ST-segment elevation in the right precordial leads (Bru-ECG) and is associated with a high risk for sudden death. However, it is unclear whether the arrhythmogenesis is caused by the mechanisms responsible for Bru-ECG. The present study investigated the risk of arrhythmias in patients with Bru-ECG by retrospectively analyzing 30 patients (28 men; mean age, 51+/-14 years) with Bru-ECG. Aborted sudden cardiac death (ventricular fibrillation or syncope) occurred in 9 patients (30%); paroxysmal atrial fibrillation was present in 9 (30%) patients in addition to malignant ventricular arrhythmias, and some type of arrhythmic event (aborted sudden cardiac death or paroxysmal atrial fibrillation) occurred in 15 patients (50%). Of all the arrhythmic events, 93% occurred at night or early in the morning, and 92% had pronounced ST-segment elevation. These results suggest that Bru-ECG may be associated not only with an increased risk of ventricular tachyarrhythmias but also with an increased risk of paroxysmal atrial fibrillation, and that the arrhythmogenesis may be related to the pronounced ST-segment elevation.

Adult↗